[PDF][PDF] Critical regulation of early Th17 cell differentiation by interleukin-1 signaling

Y Chung, SH Chang, GJ Martinez, XO Yang, R Nurieva… - Immunity, 2009 - cell.com
Y Chung, SH Chang, GJ Martinez, XO Yang, R Nurieva, HS Kang, L Ma, SS Watowich
Immunity, 2009cell.com
T helper (Th) 17 cells have been recently discovered in both mouse and human. Here we
show that interleukin-1 (IL-1) signaling on T cells is critically required for the early
programming of Th17 cell lineage and Th17 cell-mediated autoimmunity. IL-1 receptor1
expression in T cells, which was induced by IL-6, was necessary for the induction of
experimental autoimmune encephalomyelitis and for early Th17 cell differentiation in vivo.
Moreover, IL-1 signaling in T cells was required in dendritic cell-mediated Th17 cell …
Summary
T helper (Th) 17 cells have been recently discovered in both mouse and human. Here we show that interleukin-1 (IL-1) signaling on T cells is critically required for the early programming of Th17 cell lineage and Th17 cell-mediated autoimmunity. IL-1 receptor1 expression in T cells, which was induced by IL-6, was necessary for the induction of experimental autoimmune encephalomyelitis and for early Th17 cell differentiation in vivo. Moreover, IL-1 signaling in T cells was required in dendritic cell-mediated Th17 cell differentiation from naive or regulatory precursors and IL-1 synergized with IL-6 and IL-23 to regulate Th17 cell differentiation and maintain cytokine expression in effector Th17 cells. Importantly, IL-1 regulated the expression of the transcription factors IRF4 and RORγt during Th17 cell differentiation; overexpression of these two factors resulted in IL-1-independent Th17 cell polarization. Our data thus indicate a critical role of IL-1 in Th17 cell differentiation and this pathway may serve as a unique target for Th17 cell-mediated immunopathology.
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